The objectives of this proposal are to study some of the biochemical and immunological factors that may be involved in the pathogenesis of acute liver injury and the perpetuation of chronic liver disease. We plan to: 1. Study the role of cell mediated immunity in acute and chronic viral and drug induced liver diseases; 2. Characterize a serum inhibitor of cytotoxic lymphocytes and the composition and effect of circulating immune complexes in viral and drug induced hepatitis; 3. Determine the role of humoral and cell mediated immunity in an experimental model system of murine hepatitis; 4. Study the ultrastructural and biochemical changes in Reye's syndrome and search for hepatotoxic factors; 5. Determine the role of proteases and the effect of human alpha-1-antitrypsin on liver injury in an experimental model and in vitro systems; 6. Characterize the abnormalities in amino acid metabolism that may be responsible for coma associated with massive liver injury and determine the therapeutic effect of specific amino acids. BIBLIOGRAPHIC REFERENCES: Carter, E.A., Wands, J.W., Alpert, E. and Isselbacher, K.J. On the measurement and specificity of serum DNA polymerase activity. New Eng. J. Med. 296:173-174, 1977. Wands, J.R., LaMont, J.T., Mann, E. and Isselbacher, K.J. Arthritis associated with intestinal bypass procedures for morbid obesity: Complement activation and characterization of circulating cryoproteins. New Eng. J. Med., 294:121-124, 1976.